alpha-phenyl-alpha(4-tertiary amino alkoxyimino-2,5 - cyclohexadiene - 1 - ylidene)acetonitriles and process for preparing them



zigtwleiiil 3,417 893 u-PHENYL-ct(4-TERTIARY AMIN() ALKOXYIMINO= 2,5 CYCLOHEXADIENE 1 w YLIDENE)ACETO- NITRILES PROCESS FOR PREPARING THEM Gunther Seidl, Frankfurt am Main, and Georg Nesemann,

Lorsbach, Taunus, Germany, assignors to Farbwerke Hoechst Aktiengesellschaft vormals Meister Lucius &

Bruning, Frankfurt am Main, Germany, a corporation of Germany No Drawingo Filed Feb, 16, 1965, Ser. No. 433,197

Claims priority, application Germany, Feb. 18, 1964,

F 42,032 8 Claimsa (CL 260-494.?)

ABSTRACT OF THE DISCLOSURE Compounds of the formula R3 R2 wherein R is a tertiary aminoalkyl and R R and R are chlorine or methyl, said compounds having fungicidal and parasiticidal properties.

The present invention relates to a process for preparing quinone-oxim compounds corresponding to the general Formula I CN R2 at wherein R is tertiary aminoalkyl having 2-3 carbon atoms between the hetero atoms and R to R are chlorine or methyl. The process comprises alkyiating a quinone-oximof the general Formula E in which R to R, have the meanings given above, with an alkylating agent of the general. Formula 111 in which R has the meaning given above and X stands for a halogen atom, an alkyl sulfonate group, an arylsulfonate group, or an alkylcarbonate group.

The starting compounds of the general Formula II can be obtained according to J. Org. Chem. 26, 4270 (1961), by condensation of aromatic nitro compounds with benzyl cyanides. There can be used, for instance:

. jQfiQ j ERENCE SEARGH 3,417,093 Patented Dec. 17, 1968 hexadiene ring in 2-, 3-, 5- or 6-position. [Nomenclature according to J. Org. Chem. 26, 4270 (1961)].

As starting compounds of the general Formula III alkylation is carried out at a temperature of between 10 and 160 C., preferably between 20 C. and C. The period of reaction amounts to 1 to 15 hours. The molecular proportion of the components used may be varied within wide limits; preferably the oxim derivative II is reacted with an equivalent amount or with an excessive amount up to 50% of the alkylating agent and with an amount of 1 to 1.5 equivalents of the acid binding agent.

The reaction solution is then concentrated or, if solvents miscible with water are used, water is added and the re action product is purified by chromatography. When preparing dialkylamino-alkyl compounds in a solvent immiscible with water the solution is shaken out with dilute acid, such as sulfuric acid or hydrochloric acid and the base is separated from the aqueous phase by adding an excessive amount of sodium hydroxide solution.

In contradistiction to the alkylation of oxims hitherto described which always leads to O-oxim ethers in additiOIl to nitrones, i.e. to O-alkylation products in addition to N-alkylation products (cf. for instance, I. Am. Chem. Soc. 84 (1962), pages 1197-1204, especially page 1198, column 1) the reaction carried out according to the method of the present invention by which quinone-oxims are alkylated, surprisingly takes a completely uniform course. As can be proved by infrared spectroscopic examinations, exclusively O-oxim ethers are obtained in goods yields.

The products obtained by the process of the present invention can be used for combating fun i and parasitcs in which R'fin the general formula I represents a basically substituted alkyl radical, show a very good efliciency on a large number of fungus strains such as skin fungi and rotting fungi as well as on. parasites such as trichomon-a'ds; in numerous products obtained according to the process of the present invention the inhibiting concentration is already within the range of l microgram (7) per milliliter. The serum factor is low. It is, for instance, possible to prepare a 1%-solution in propanoldimethylformamide-ethanol in order to treat interdigital mycoses.

The preparatiosr i can likewise be incorporated into ointments and emul 10118. When operating in this way, the addition of hydro-cortisone or prednisolone showing anti-phlogistic action may favour and improve the therapeutic effect in the case of weeping and eczematized mycoses. When dry, squamous mycoscs are concerned, the therapeutic effect can be increased by the addition of salicylic acid.

It is likewise possible to treat bovines suffering from trichophyton infections with a solution of 15% strength in dilute dimethyl-sulfoxide or isopropanol.

Because of the high action the preparations exert on .Aspergillus niger, they are likewise suitable for technical use, For instance, it added the dyestuffs and painting ma terials, they inhibit the moulding of the walls. By spraying hen houses with a 1% solution in dimethyl-formamide of 70% strength, the spreading of poultry aspergillosis can be combated. The products are likewise active on other micro-organisms such as Candida and phytopatho genie fungi.

The following examples serve to illustrate the invention but they are not intended to limit it thereto:

Example 1.-a-Phenylx (4-fi-piperidino-ethoxy-imino- 2,5 -cyclohexadienel-ylidene) acetonitrile 22 grams of quinone-oxim 1 are alkylated and worked up with 1.2 equivalents of piperidino-ethyl-chloride as described in. Example 6. 25' grams of piperidino-alkylether are obtained in the form of a yellow-red oil whose oxalate melts at l46147 C. (The naphthalene-1,5-disulfonate melts at 189191 C.)

Example 2.u-Phenyl @(4 gamma-dimethylaminopropyloxy imino 2,5 m cyclohexadiene-l-ylidene) acetonitrile (a) According to the method described in. Example 6,

22 grams of quinone-oxim 1 are reacted with 1.2

equivalents of 'y dimethylaminopropyl-chloride and worked up. 26 grams of dimethylamino-propyl-ether are obtained in the form of a yellow-red oil. The oxalate melts at 177 to 179 C, the naphthaleue-1,5-disulfonate at 192196 C. The quaternary salt with methyl-iodide melts at 156-458 C.

(b) 22 grams of quinone-oxim 1 are heated together with 2.5 grams of di-y-dimethylaminopropyl-carbonate and 2 grams of anhydrous potassium carbonate for 3 hours at 150 C1 The reaction mixture is poured into water, shaken. out with ether and the ether solution is concentrated. 18 grams of dimethyl-aminopropyl-ether are obtained whose oxalate melts at 177-179 C. The mixed melting point of the oxalate obtained. according to Example 8:: shows no depression.

Example 3.-a-Phenyl-a.(4-gamma-pyrrolidino-propyb oxy-imino-2,5-cyclohexadiene-l-ylidene) acetonitrile According to the method described in Example 6, 22

grams of quinone-oxim 1 are reacted with 1.2 equivalents of 'y-pyrrolidino-propyl-chloride. The pyrrolidino-propylether is obtained in a yield of 19 grams as a red oil. The oxalate melts at 148-151 Example 4.oc u Phenyl-m(3-chloro-4gamma-dimethyl amino-propyloxy imino-2,S-cyclohexadiene-l-ylidene) acetonitrile 25.7 grams of 4-oxo-a-phenyl-3-chloro-2,5-cyclohexadiene-A ,u-acetonitrile-oxim are alkylated with dimethyl amino-propyl-chloride according to the method described in Example 6. 27 grams of the above-mentioned base are obtained, whose oxalate melts at 164-166 C. The quater= nary salt with. methyl-iodide melts at 174-176" C.

Example 5.--a-(4-chlorophenyl)-u-(2-chl0ro-4-gamma dimethylarnino propyloxy-imino-2,5-cyclohexadiene 1-ylidene)acetonitrile By alkylation of 29 grams of 4-oxo-a.-4 chlorophenyl 2 chloro-Z,5-cyclohexadiene-A ,a-acetonitrile-oxirn with 'y-dimethylamino-propyl-chloride according to the method described in Example 6, 18 grams of the base are obtained whose oxalate melts at 138-141 C.

Example 6.m (3,4 dichlorophenyl) -u.-(4-gamma--di= methylamino-propyloxy-imino 2.5 Q cyclohexadiene l" ylidene acetonitrile The alkylation of 58 grams of 4-oxo-ct-3.4--dichlorophenyl-Z,S-cyclohexadiene-A ,rx-acetonitrile-oxirn with di methylamino-propyl-chloride is carried out as described Example 6. 48 grams of the above-mentioned base are obtained which are purified by chromatography on aluminium oxide. The oxalate melts at 159-162 C., the quaternary salt with methyl-iodide at 195-196 C.

Example 7.-a-(2,4dichlorophenyl) D a (4-gamrna di methylamino propyloxy-imino-2,S-cyclohexadiene-1 ylidene) acetonitrile The alkylation of 58 grams of 4-0X0-a-Z ,4'-diChlOI0 phenyl-2,5-cyclohexadiene-A ,a.-acetonitrile-oxim with di= methylamiuo-pro pyl-chloride is carried out as described in Example 6. 60 grams of the above-mentioned base are obtained which are purified by chromatography on aluminium-oxide. The oxalate melts at 134-135 (3.. the quaternary salt with brornacetic acid-ethyl-ester melts at 116-118 C Example 8. x Phenyl-ot(3-methyl-4-gamma-dimethyl amino propyloxy-imino-Z,5-cyclohexadiene- 1-ylidene) acetonitrile The alkylation of 54.3 grams of 4-oxo-vr-phenyl-3= methyl-2,5-cyclohexadiene-A ,m-acetonitrile-oxim with. -ydimethylamino-propyl-chloride is carried out as described in Example 6. 61 grams of the above-mentioned base are obtained whose oxalate melts at 154156 C. The quater= nary salt with methyl-iodide melts at 194--196 C.

We claim:

1. a Phenyl-a(4-;9-piperidino-ethoxyimino-2,5 cyclo= hexadienel-ylidene) acetonitrile.

2. a Phenyl-u(4-gamma-dimethylamino propyloxyimino-2,5-cyclohexadiene- 1 -ylidene) acetonitrile.

3. a Phenyl-ot(4-gamma-pyrrolidino-propyloxy-imino- 2,5-cyclohexadiene-l-ylidene) acetonitrile.

4. m-PhI1Yl-0t(3-Chl0f0 4 gammmdimethylaminm propyloxy imino-2,5-cyclohexadiene-l-yliclene)acetoni= trile.

5. on (4-ChlOI'OphfiI1Yl)'lZ-(Z-ChIQI'O u 4- gamma-db methylamino propyloxyimino-2,5-cyc1ohexadiene l-yl-= idene) actonitrile.

6. a.(3,4-dichlorophenyl) or. (4 gamma-dimethyl amino-propyloxy-imino 2,5 cyclohexadiene-l-ylidene) acetonitrile.

7. a-(2,4-dichlorophenyl) n or (4 gamma-dimethyhamino-propyloxyirnino 2,5 m eyclohexadiened.ylidene) acetonitrile.

8. or-P-henyl-a(3-methyl 4 gamma-dimethylamino propyloxy n imino-2,5-cyclohexadien.e-1-ylidene)acetonitrile.

References Cited JOSE TOVAR, Assistant Examiner,

US. Cl. XQR, 

